Time Of Testing Research Articles

Prevalence Estimates of Cytochrome P450 Phenoconversion in Youth Receiving Pharmacotherapy for Mental Health Conditions.

Pharmacogenetics-predicted drug metabolism may not match clinically observed metabolism due to a phenomenon known as phenoconversion. Phenoconversion can occur when an inhibitor or inducer of a drug-metabolizing enzyme is present. Although estimates of phenoconversion in adult populations are available, prevalence estimates in youth populations are limited. To address this gap, we estimated the prevalence of phenoconversion in 1281 youth (6-24 years) receiving pharmacotherapy for mental health conditions and who had pharmacogenetics testing completed for four genes (CYP2B6, CYP2C19, CYP2D6, CYP3A4). Self-reported medication and cannabidiol/cannabis use were collected at the time of pharmacogenetics testing. Nearly, half (46%) of the cohort was estimated to be phenoconverted for one of the four genes examined. Comparison of metabolizer phenotype frequencies before and after adjustment for phenoconversion showed significantly more youth had actionable phenotypes for CYP2C19 (60.3% vs. 69.1%; P =< 0.001), CYP2D6 (49.3% vs. 63.0%; P =< 0.001), and CYP3A4 (8.5% vs.12.2%; P = 0.003) after phenoconversion adjustment. Of youth who were phenoconverted, 24% had a change in their metabolizer phenotype that would lead to current pharmacogenetics-based prescribing guidelines recommending a change to standard prescribing (dose adjustment, alternative medication). Our findings indicate a high prevalence of cytochrome P450 phenoconversion among youth receiving pharmacotherapy for mental health conditions. Adjustment for phenoconversion should be considered when implementing pharmacogenetics testing in youth populations to improve the clinical utility of this testing in practice.

Motor functioning during early recovery after childhood Arterial ischemic stroke is associated with intellectual abilities

Motor impairments are one of the most common adverse outcomes after childhood arterial ischemic stroke (C-AIS), yet their relationship with intellectual abilities is not yet well understood. This study examined associations between intellectual abilities and motor functioning and clinical features associated with motor impairment. Participants were 34 children with C-AIS. Motor functioning was assessed with the Pediatric Stroke Outcome Measure sensorimotor subscale at two timepoints: early recovery (between 30 days post-stroke and 1 year) and closest to time of neuropsychological testing. Intellectual abilities were measured using the Wechsler Intelligence Scale for Children 4th or 5th edition. Motor functioning during early recovery was significantly associated with intellectual functioning, verbal abilities, perceptual reasoning abilities, and processing speed. Motor functioning closest to time of neuropsychological testing was associated with processing speed. There were more children with subcortical lesions with no/mild motor deficit, whereas there were more children with cortical + subcortical lesions with moderate/severe motor deficits. Associations between motor functioning during early stroke recovery and intellectual abilities may be related to neuroplastic changes post-injury, resulting in early motor deficits and affecting subsequent development of intellectual abilities through hierarchical maturational processes, whereas motor functioning closer to neuropsychological testing reflects maturational recovery processes augmented by intervention.

A MALDI-TOF MS-based multiple detection panel of drug resistance-associated multiple single-nucleotide polymorphisms in Candida tropicalis.

Candida tropicalis is one of the main causes of invasive candidiasis. Rapid identification of antifungal resistance is crucial for selection of an appropriate antifungal to improve patient outcomes. Mutations at specific loci are strongly correlated with resistance to antifungal agents. In this study, we developed a multi-single-nucleotide polymorphism (SNP) panel to accurately identify 36 mutation sites across seven genes of C. tropicalis that are associated with resistance to azoles and/or echinocandins. Ten isolates were selected to test repeatability, and another 20 isolates of C. tropicalis were selected to validate consistency. Intra-assay and inter-assay repeatability of the panel was 100%, with the loci accuracy being 99.44% (716 of 720). Furthermore, 109 isolates were examined for clinical research, and the most commonly detected mutations were G751A and A866T of UPC2, A491T of TAC1, and A395T and C461T of ERG11. The G751A and A866T mutations of UPC2 as well as the A395T and C461T mutations of ERG11 co-existed. The SNP panel enables identification of specific mutations at critical sites of drug-resistant strains to facilitate the rapid selection of appropriate antifungal agents and efficient monitoring of the regional epidemiological trends of resistance of C. tropicalis.IMPORTANCEC. tropicalis infections pose a growing global public health challenge, with mortality rates approaching 40%. C. tropicalis is one of the top four Candida spp. responsible for candidiasis, particularly in the Asia-Pacific region and Latin America, notably affecting patients with neutropenia and malignancies. The azole resistance rate of C. tropicalis ranges from 0% to 30%. Between 2009 and 2018, the China Hospital Invasive Fungal Surveillance Network reported an increase in fluconazole and voriconazole resistance from 5.7% to ~30%. Although resistance to echinocandins and amphotericin B remains low, multi-resistance to echinocandins and azoles has been observed. Current methods for detecting drug resistance are limited by the long turnaround time of antifungal susceptibility testing, low throughput of Sanger sequence to target resistance mutations, complex data analysis, and high costs of second-generation sequencing. We developed and validated a rapid, high-throughput, and cost-effective panel to detect and monitor drug-resistance mutations of C. tropicalis.

Recorded Word Recognition Testing Is Worth the Time.

The goal of this study was to provide evidence of the inherent variability associated with monitored live voice (MLV) presentation methods and encourage audiologists to more closely follow best practice of using recorded stimuli. To accomplish the goal, administration times for word recognition testing were compared between MLV and MP3 recorded stimuli presented directly from an audiometer (computer assisted, CA). Furthermore, the variability of administration time across testers was evaluated. Fifty-word NU-6 lists were presented via MLV and CA to listeners with typical hearing (TH; defined as a four-frequency [500, 1000, 2000, and 4000 Hz] pure-tone average [PTA] of 20 dB HL or better) and hearing loss (HL; defined as a four-frequency PTA poorer than 20 dB HL). Audiologists and doctor of audiology students administered the word lists. Administration times were compared between the two presentation methods (MLV and CA). MLV administration time was significantly shorter than CA presentation time for both the TH and HL groups. There was also a significant difference in word recognition scores (WRS) between the TH and HL groups only when using the CA method. Most notably, there was significantly more variability in the administration time for MLV presentation across testers compared to the CA method. Data were compared to Mendel and Owen (2011), and MLV administration time was found to be significantly shorter than CA and compact disk (CD) administration time. Despite the shorter average administration time for MLV presentation compared to CA or CD, the significant variability in administration time among individual testers limits the clinical value of the test results. In addition, WRS for those with hearing loss were significantly poorer than those with TH when using CA but not for MLV, indicating that MLV is not sensitive to the presence of sensorineural hearing loss. Thus, using recorded word recognition is strongly recommended.

Hesperidin produces antidepressant effects by activating AMPA receptor: enhancing synaptic proteins to promote hippocampal neuronal activities.

Hesperidin treatments reduce depressive symptoms in mouse models of depression, but the mechanism that mediates its antidepressant effects is unclear. This study shows that hesperidin exerts its antidepressant effects by activating α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor to promote synaptic and neuronal function in the hippocampus. The optimal dose of hesperidin (10 mg/kg) for the antidepressant potential was determined after 7 consecutive days of treatments, demonstrating decreased latency to eat and increased food consumption in novelty suppressed feeding, and decreased immobility time in tail suspension test (TST). Moreover, the optimal dose also reversed the depressive phenotypes of Institute of Cancer Research mice exposed to chronic unpredictable mild stress (CUMS), including reduced immobility time in the TST and increased sucrose preference in the sucrose preference test. In addition, hesperidin increased the expression of AMPA receptor protein (Glur1) and synaptic proteins (BDNF, PSD95, synapsin1) in the hippocampus of CUMS-exposed mice. Furthermore, inhibition of AMPA receptor activity by NBQX blocked the effect of hesperidin in reversing the depressive phenotypes, upregulated the expression of synaptic proteins (BDNF, PSD95, synapsin1) and cFOS-positive cells in the hippocampus, and increased the number of Ki67-positive cells in the dentate gyrus of the hippocampus of CUMS-exposed mice. These results help to further understand the antidepressant mechanism of hesperidin and provide new ideas for the future development of antidepressant drugs.

Long-term Administration of High-Dose Methylphenidate Impairs Spatial Memory and Induces Neurodegeneration in the Hippocampus

Background: Methylphenidate hydrochloride (MPH) is used as a first-line treatment for attention-deficit/hyperactivity disorder. Nonetheless, there are a few studies regarding the relationship between memory and hippocampal neuron changes following long-term MPH treatment. Objectives: This study aimed to investigate the effects of pathological changes on memory following long-term MPH treatment. Methods: Forty rats were randomly and equally divided into four groups based on dosages. Animals underwent 0.6, 2.5 (low doses), or 10 (high dose) mg/kg MPH or saline (control) per day for 28 days. The Morris water maze (MWM) test was conducted at two time points: Two hours and four weeks after initiating MPH administration. The two-hour test evaluated single dose effects of MPH on memory, while the four-week test assessed long-term administration of MPH effects on memory performance. Finally, the brains were removed and pathological alterations in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the hippocampus were investigated. Results: Single-dose administration of 10 mg/kg MPH decreased the latency time in the MWM test, while long-term administration of MPH increased the latency time. Furthermore, histopathology results showed that MPH at doses of 2.5 mg/kg and 10 mg/kg significantly increased the percentage of neurodegeneration in both the CA1 and DG regions compared to controls. Conclusions: Our findings show that a high single dose of MPH improves memory in rats. However, long-term administration of high dose of MPH impaired memory; such impairment may be associated with the neurodegeneration in the pyramidal layer cell of the CA1 and the granular layer cell of the DG.

The Effectiveness of Focus of Attention in Static Balance and Functional Ability of Chronic Ankle Instability: A Pilot Study

Objectives: The focus of patients’ attention during the physiotherapy program has been reported to affect the rehabilitation goals. The study aimed to investigate the effectiveness of an external focus of attention (EFA) on static balance and functional ability in individuals with chronic ankle instability (CAI). Methods: Fourteen subjects with CAI, aged from 19 to 25 years, were randomly assigned to two groups: external and internal focus of attention (IFA) group. The outcome measures of the study were static balance and functional ability. A pre-intervention evaluation was performed. Following instructions to an external or an IFA, subjects practiced on a balance board 3 times per week for 4 weeks. At the end of each week, they performed evaluation tests, including a time balance test, foot lift test, side hop test, figure-8 test, and star excursion balance test (SEBT). Parametric (mixed analysis of variance) and non-parametric analysis (the Mann–Whitney and Friedman tests) were performed between measurements and groups. Results: The intervention program showed a statistically significant improvement in static balance and functional ability in both groups. The results indicated the main effect of time (F(2.488, 29.855)=43.880, P&lt;0.001). For the time in balance test, analysis of variance revealed a main effect of time (F(2.571, 30.855)=11.188, P&lt;0.001). Regarding the SEBT, every direction indicated a main effect of time for both groups. No significant differences between the two groups were found in static balance and functional ability. Discussion: Even though there were no statistically significant differences between the two groups, both types of focus of attention contributed to the improvement of static balance and functional ability, which may reveal an increase in motor control and neuromuscular ability of the subjects with CAI.

Cornus mas (Cornelian Cherry) Exerts Neuroprotective Effects on Cerebral Ischemia/Reperfusion Injury via Anti-Inflammatory and Antioxidant Properties

Background: Stroke is one of the most important causes of mortality and disability in the world. Over 80% of strokes are ischemic, resulting from blockages in cerebral arteries. Increasing evidence suggests that enriching the diet with nutritional antioxidants could decrease brain damage and enhance cognitive function. Cornelian cherry has anti-inflammatory and antioxidant properties and is introduced as a potential source of active ingredients, like anthocyanins, vitamin C, phenolic compounds, and minerals. Objective: Our research study aimed to evaluate the neuroprotective impact of Cornus mas L. (cornelian cherry) on a rat model of Cerebral Ischemia/Reperfusion Injury (CIRI). Methods: Middle cerebral artery blockage induced CIRI for 60 minutes. After inducing CIRI, intraperitoneal injections of Cornus mas Extract (CME) were administered for 14 days in a dosedependent manner (30, 60, and 120 mg/kg body weight). The effects of CME on learning and memory recovery were evaluated using a shuttle box behavioral test. Two weeks following CIRI, several factors of oxidative stress, such as nitrite (NO2-), Ferric ion Reducing Antioxidant Power (FRAP), and Malondialdehyde (MDA), were measured in the hippocampal tissues and serum. Anti-inflammatory genes, such as miR-125b, and the target genes (TNF-α and iNOS) were evaluated via real-time PCR assay. Additionally, neural damage in the CA1 and CA3 regions of the hippocampus was assessed using Hematoxylin and Eosin (H&amp;E) staining. Results: The avoidance time in the shuttle-box behavior test supported our finding that CME exhibited improved fear memory. Furthermore, it increased the CA1 and CA3 hippocampal post-stroke pyramidal cell layers. Levels of NO2- and MDA were decreased, and FRAP was considerably increased in both the hippocampus and serum by CME. Additionally, CME increased miR-125b expression, while modulating TNF-α and iNOS production in the hippocampal regions. Conclusion: Based on our findings, we can conclude CME to possess antioxidant and antiinflammatory properties, which confer neuroprotective potential against CIRI, thereby protecting neurons from ischemic death.

Enhancing the Integration of Pre-Emptive Pharmacogenetic (PGx) Testing in Primary Care: Prioritizing Underserved Patients’ Preferences in Implementation

Background/Objectives: The integration of pharmacogenetic (PGx) testing into primary care has not been widely implemented, despite its benefits for patients and providers. PGx testing could also reduce health disparities as patients with lower healthcare access are prescribed higher proportions of medications with PGx guidelines. Little is known about the preferences of patients who have experienced PGx testing to inform implementation across the care process. This qualitative study aimed to refine implementation by capturing patient preferences on (1) testing and prescription timing, (2) patient–clinician discussion of results during post-test counseling, and (3) usability of a card during results dissemination. Methods: Interviews were conducted with 25 primary care patients from clinics primarily serving medically underserved populations. Interview transcripts were thematically analyzed using a constant comparative approach. Results: While patients supported both reactive and pre-emptive testing, they valued pre-emptive PGx testing because it is proactive for future health needs, expedites treatment, and is convenient. Patients’ preferences for receiving prescriptions depended on several factors: having immediate access to needed medications, avoiding experiencing medication side effects and interactions, avoiding taking ineffective medications, and avoiding inconveniences. Patients identified three issues critical to patient–clinician interactions when receiving testing results: information specific to medications, clarification and further information about their results, and enhanced clinician accessibility related to the results. Lastly, they liked that the results card could facilitate discussions with clinicians and was informative and convenient but said it lacked clarity. Conclusions: These findings should inform implementation strategies for integrating PGx testing in primary care for underserved patients.

Oxford Shoulder Instability Score: cross-cultural adaptation into Spanish and analysis of its methodological quality

BackgroundOxford Shoulder Instability Score (OSIS) is a patient reported outcome measure designed specifically to assess functional difficulties resulting from shoulder instability. The main aim of this study was to cross-culturally adapt the OSIS to Spanish. Secondary, it aimed to analyse its methodological quality.MethodsA cross-cultural adaptation to Spanish has been carried out following the recommendations of COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) with a sample of 167 cases of shoulder instability. Inclusion criteria were: subjects with instability symptoms in at least one shoulder with or without clinical diagnosis; aged between 18 and 60. The following psychometric properties were evaluated: validity (construct, internal and external), reliability (internal consistency, test-retest and measurement error), discriminant ability and feasibility. The methodological quality was addressed with Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and COSMIN Risk of Bias checklist (COSMIN RoB).ResultsThe construct validity obtained an OSIS correlation with the Simple Shoulder Test of r = 0.636 and with the Western Ontario Shoulder Instability of r = 0.80. The unidimensionality of the OSIS was confirmed through second-order factor analysis. Cronbach’s alpha and intraclass correlation coefficient were both 0.93 (IC95%: 0.91–0.94). Standard error of measurement was 0.70, and the percentage of error and smallest detectable change were 1.46% and 1.94, respectively. No floor or ceiling effects were found. Assessing feasibility of OSIS, the participants answered all questions, had no questions and completion time was: mean 2 min 30 s; SD ± 1 min. Regarding methodological quality, the study showed low risk of bias in the areas of patient selection, index test, reference standard and flow and timing, as well as low concern regarding applicability in the domains of patient selection, index test and reference standard according to QUADAS-2. In relation to COSMIN RoB, all psychometric properties, except for content validity, obtained very good results.ConclusionsThe Spanish version of OSIS offers valid, reliable and feasible functional outcome measures for Spanish-speaking subjects with shoulder instability, based on its psychometric properties and its methodological quality.

SIMTAM: Generation Diversity Test Programs for FPGA Simulation Tools Testing Via Timing Area Mutation

Field-Programmable Gate Array (FPGA) timing simulation is essential in electronic circuit design, allowing for the verification of timing characteristics like delays and clock frequencies. However, bugs in timing simulation tools can lead to inaccurate results, potentially causing designers to miss critical issues in chip performance. Traditional testing methods often fall short in thoroughly assessing these tools, as current FPGA testing primarily focuses on synthesis and behavioral simulation, neglecting timing aspects. To address this issue, we propose SIMTAM for testing timing simulation tools. Specifically, SIMTAM consists of three components: equivalent delay region construction, diversity program segment generation, and differential testing. Given a seed circuit design file written by hardware description language such as Verilog, the delay region construction component randomly identifies delay structures for inertial delay in the design file to construct equivalent delay sleep regions. In the sleep region, the simulator skips the signal pulse whose width is less than the specified delay, thus ensuring the equivalence of the variations. The diversity program segment generation component combines Verilog expressions using generation operators and inject them into the sleep region to generate diverse design files. The differential testing component compares the seed and variant design files to find compilation inconsistency issues. In five months, SIMTAM reported 16 bugs to developers in two popular timing simulation tools Iverilog and Vivado; ten of which are confirmed.

The Mechanism of Propofol in Treating Depression-like Behaviors Based on Network Pharmacology and Experimental Validation

Objective: To explore the potential mechanism of propofol in improving antidepressant-like behavior through network pharmacology and animal experimental validation, providing theoretical and experimental support for the development of novel antidepressant drugs based on propofol. Methods: 1. The targets of propofol and the disease targets of depression were screened through Swiss Target prediction, Super-pred, SEA, Drugbank, CTD, GeneCards, OMIM, and TTD databases. A protein-protein interaction (PPI) network was constructed, and the core targets were screened and visualized using CytoScape 3.10.2 software. Additionally, GO and KEGG enrichment analyses of the intersection targets were performed using the Metascape database. 2. Thirty male C57BL/6 mice were randomly divided into the CON group, LH model group, and PRO treatment group, with 10 mice in each group. The sucrose preference test, forced swim test, and tail suspension test were conducted to determine whether the depression model was successfully established and to assess the improvement effect of propofol on antidepressant-like behavior. 3. The pathological morphological changes of hippocampal neurons in the three groups of mice were observed through HE staining experiments. The expression of mGluR5 protein in the hippocampus was analyzed by Western blot. Results: 1. Network pharmacology analysis indicated that propofol may exert antidepressant effects by acting on core genes such as ALB, ESR1, NFKB1, HSP90AB1, and EGFR. These core target genes were mainly enriched in biological processes such as synaptic transmission and membrane potential regulation; they involved cellular components such as GABA receptor complexes and synaptic membranes; and they included molecular functions such as neurotransmitter receptor activity. Additionally, propofol may exert antidepressant effects through signaling pathways such as neuroactive ligand-receptor interaction, morphine addiction, and GABAergic synapse. 2. Compared with the CON group, the sucrose preference rate of mice in the LH model group significantly decreased, while the immobility time in the forced swim test and tail suspension test significantly increased. Compared with the LH model group, the sucrose preference rate of mice in the PRO treatment group significantly increased, and the immobility time significantly decreased. 3. The HE results showed that compared with the CON group, the number of neurons in the LH group decreased, with loose arrangement, pycnotic and deeply stained nuclei with blurred boundaries. However, the number of necrotic neurons in the PRO group significantly decreased. The Western blot results showed that compared with the CON group, the expression level of mGluR5 protein in the LH model group significantly increased, while it significantly decreased in the PRO treatment group compared with the LH model group. Conclusion: Propofol may exert antidepressant effects by regulating the expression of mGluR5, improving antidepressant-like behavior, and reducing hippocampal neuronal necrosis.

Expanded carrier screening for 224 monogenic disease genes in 1,499 Chinese couples: asingle-center study.

Expanded carrier screening (ECS) is a preventive genetic test that enables couples to know their risk of having a child affected by certain monogenetic diseases. This study aimed to evaluate the carrier frequency for rare monogenic diseases in the general Chinese population and the impacts of ECS on their reproductive decisions and pregnancy outcomes. This single-center study was conducted between September 2022 and April 2023. An ECS panel containing 224 recessive genes was offered to 1,499 Chinese couples from the general population who were at early gestational ages or planned to conceive. Overall, 55.0 % of the individuals carried for at least one recessive condition. There were 16 autosomal recessive (AR) genes with a carrier frequency of≥1/100 and 22 AR genes with a carrier frequency of <1/100 to ≥1/200. The most common AR and X-linked diseases were GJB2-related non-syndromic hearing loss, and hemolytic anemia, respectively. Fifty-five couples (3.67 %; 1 in 27.3) were at increased risk of having an affected child with 19 pregnant at the time of testing. Of these, 10 opted for amniocentesis, and four affected pregnancies were identified, with three of them being terminated. This study not only provides valuable information about the recessive genetic landscape, but also establishes a solid foundation for couple-based ECS in a real clinical setting.

Val66Met Polymorphism of the BDNF Gene and Work Intellectual Complexity: Associations with Speed Characteristics of Cognitive Activity in Aging

The high heterogeneity of cognitive aging is explained by the influence of both genetic and environmental factors. It has been shown that increasing cognitive reserve prevents the development of aging-related cognitive impairment. Education and level of professional activity are considered external factors in the formation of cognitive reserve. BDNF (brain-derived neurotrophic factor) is a neurotrophic factor involved in the processes of plasticity of the mature brain. A polymorphism (Val66Met) of the BDNF gene is associated with differential expression of BDNF, suggesting its potential role in the on cognitive training outcomes. The associations between Val66Met polymorphism and the effectiveness of mental training caused by and work intellectual complexity throughout adult life (in our study, a comparison of scientists - SA and people not associated with professional scientific activities — NSA remain unstudied. The objective of the study was to assess the modulating effect of these factors in relation to aging-related changes in the processes of attention and figurative creativity in models that allow us to consider both the efficiency and speed aspects of activity. The study involved 257 healthy young and 162 elderly Caucasians belonging to the groups of SA and NSA. It has been shown that the Val66Met polymorphism of the BDNF gene is associated with the influence of the level of professional activity on the efficiency of cognitive functions only in elderly subjects. At a higher intensity of intellectual activity (SA), Val/Val, but not Val/Met carriers, showed a reduction in the average reaction time in the Attention network test and an increase in fluency when testing figurative creativity compared to similar indicators of elderly subjects in the NSA group. The results obtained indicate greater plasticity of cognitive functions in carriers of the Val/Val genotype and may be used for prediction and development of methods for differentiated correction of age-related cognitive decline.

Validation of a reduction in time for avian influenza virus isolation using specific pathogen-free embryonated chicken eggs.

The international gold standard for avian influenza virus (AIV) diagnosis is virus isolation (VI) in specific pathogen-free embryonated chicken eggs (ECEs). AIV isolation typically involves a 6-day turnaround, during which premises under suspicion for notifiable AIV infection are held under restriction regardless of molecular diagnoses, often with significant welfare implications. A reduction in time for negation by VI was investigated following experimental inoculation of AIV from known-positive original clinical material into ECEs. VI data derived from more than 600 case investigations from epizootics of high-pathogenicity AIV (HPAIV) in Great Britain since 2016 and from low-pathogenicity AIV (LPAIV) cases in Great Britain since 2014 were examined to support a reduction in test timing using alternative regimens. HPAIVs were isolated during the first passage, and for LPAIV VI, the second passage could be reduced to 2 days. Power analysis showed that the benefit of reducing the number of days outweighed the risk of missing a positive isolate. Limited data were available from experimental inoculations. This truncated methodology, which enables an earlier release of restrictions, may substantially ease the economic implications of restriction. It could also reduce bird welfare implications and improve international standards without loss of test performance.

Quantifying the association between PM2.5 air pollution and IQ loss in children: a systematic review and meta-analysis

BackgroundA growing body of epidemiologic and toxicologic literature indicates that fine airborne particulate matter (PM2.5) pollution is neurotoxic and threatens children’s neurobehavioral development, resulting in reduced cognitive function. Understanding the magnitude of this effect is critical for establishing public health policies that will protect children’s health, preserve human capital, and support societal progress.ObjectiveTo quantify the association between ambient PM2.5 air pollution and loss of cognitive function in children, as measured by Intelligence Quotient (IQ) scores, through a systematic literature review and meta-analysis.MethodsFollowing PRISMA guidelines, we conducted a systematic literature search across seven databases: Agricultural and Environmental Science, BIOSIS Citation Index, Embase, GreenFILE, PubMed, Scopus, and Web of Science to identify original scientific studies that investigated the impact of PM2.5 exposure during pre-and postnatal periods on IQ loss during childhood. Using data from studies included for final review, we conducted a meta-analysis, using a random effects model to compute a beta coefficient that quantifies the overall effect of PM2.5 exposure on Full-Scale IQ (FSIQ), Performance IQ (PIQ), and Verbal IQ (VIQ).FindingsOf the 1,107 unique publications identified, six studies met the inclusion criteria for final review, representing 4,860 children across three continents (North America, Europe, and Asia). The mean PM2.5 concentration across all studies was 30.4 ± 24.4 µg/m3. Exposure timing ranged from the prenatal period to mid-childhood. Children were an average of 8.9 years old at the time of cognitive testing. We found that each 1 µg/m3 increase in PM2.5 concentration is associated with a -0.27 point change in FSIQ (p < 0.001), 0.39 point change in PIQ (p = 0.003), and -0.24 point change in VIQ (p = 0.021).ConclusionThrough a systematic review and meta-analysis, we identified a statistically significant relationship between increased exposure to PM2.5 air pollution and reduced cognitive function in children, with the most pronounced impact on PIQ. This analysis will enable estimation of the burden of adverse neurobehavioral development attributable to PM2.5 in pediatric populations and will inform local and global strategies for exposure prevention.

Improving Turnaround Times for Routine Antimicrobial Sensitivity Testing Following European Committee on Antimicrobial Susceptibility Testing Methodology in Patients with Bacteraemia.

Background/Objectives: Bacteraemia can be fatal without antibiotic intervention. Antibiotic Susceptibility Testing (AST) provides the necessary information for targeted antibiotic therapy; however, the traditional method using disc diffusion can take over two days from a positive blood culture. Inappropriate empiric therapy is associated with increased mortality and increased antibiotic resistance, highlighting the need for more rapid turnaround times for AST. By making changes to an established method, turnaround times can be reduced. Methods: Eighty-two patient positive blood culture samples were collected from January to April 2022, representing the range of common bacteria causing sepsis. This followed the normal methodology in the laboratory of inoculating agar from positive blood cultures in preparation for European Committee on Antimicrobial Susceptibility Testing (EUCAST) disc diffusion AST method. EUCAST methodology outlines that disc diffusion should be performed on isolates from an overnight culture of 16-24 h. This study looked at comparing disc diffusion results from cultures with 6 h of incubation to those with incubation times of 24 h, after organism identification by MALDI-ToF. Results from 6-h and 24-h cultures were compared by disc zone sizes and by interpreted susceptibility reading following EUCAST guidelines of sensitive, resistant, susceptible with increased exposure, or an area of technical uncertainty. Results: A total of 99.65% interpreted susceptibility readings matched across all organisms to all relevant antibiotics, with an average zone size difference of 1.08 mm between results from 6 h versus 24 h cultures. Conclusions: This method offers a non-automated way of using the traditional disc diffusion method, reducing turnaround times while still producing reliable and accurate results. This would mean validated ASTs can be set up in the same day as a blood culture flags positive rather than waiting for a longer culture. As this method is widely used within the laboratory already, it would mean that additional training is not required, as the process is the same, and only incubation time varies. This would positively impact patient outlook due to the shorter use of empiric therapy, and benefit antimicrobial stewardship (AMS).

New approach to reduce analysis time of thermal response test: Active thermal response test using linear heat optical fiber sensor

This study introduces an innovative approach to reduce the analysis time of thermal response tests (TRTs) by employing an active TRT using a linear heat optical fiber sensor. Conventional TRTs require prolonged heating periods, making them time-consuming and resource-intensive. This research focuses on comparing conventional and active TRTs using computational fluid dynamics (CFD) simulations to validate the accuracy and efficiency of the proposed method. The active TRT method demonstrated the potential to shorten heating time while maintaining accurate thermal conductivity measurements. The findings reveal that the difference in thermal conductivity estimation between 15 and 48 h is only 0.03 W/(m∙K), indicating stable results with shorter testing times compared to the conventional TRT. Although stable results were obtained, uncertainties persist due to field conditions and measurement errors. To address this, an approximate equation was proposed for estimating thermal conductivity using the Relaxation Time of Temperature (RTT) method, which has been validated in previous studies through ground recovery temperatures. Future work will involve conducting field Active TRT to verify the accuracy of this method in reducing TRT duration.

Hepatitis C Virus Testing Among Perinatally Exposed Children: 2018 to 2020.

To assess the frequency of hepatitis C virus (HCV) testing among a population-based cohort of perinatally exposed children and identify factors associated with testing. Using a population-based surveillance cohort of perinatally exposed children born from 2018 to 2020 from 4 US jurisdictions (Georgia; Massachusetts; Allegheny County, Pennsylvania; and Los Angeles County, California), we describe the frequency, timing, and type of HCV testing among children and identify characteristics associated with having an HCV test result by the age of 2 to 3 years. Data were obtained from electronic laboratory reporting, vital records, and medical records. Of 803 perinatally exposed children, 7 (1%) died before the age of 24 months. Of 796 children, health departments were unable to find medical records or laboratory reports for 181 (23%). Among those with medical record abstraction at 24 months or testing reported before the age of 3 years (n = 615), 50% had an HCV test. The majority (70% of those tested) were tested for HCV antibodies at the age of 18 months or later, although 9% had an HCV nucleic acid test at ages 2 to <6 months. No characteristics examined were found to be significantly associated with having testing reported. In this surveillance report, we identify the gaps in current testing among children perinatally exposed to hepatitis C. Provider education and resources for health departments for follow-up and linkage to care can improve the identification of children requiring treatment, a vital piece of HCV elimination.

Ellagic acid(EA) ameliorates Alzheimer's disease by reducing Aβ levels, oxidative stress and attenuating inflammation

BackgroundEllagic acid (EA) serves as a pivotal coenzyme for various dehydrogenases, influencing diverse biological processes. Recognized for its potential in impeding disease progression, EA's effectiveness and mechanism in treating 5xFAD remain elusive. Aim of the studyThis study aims to investigate EA's potential roles and underlying mechanisms in mitigating symptoms associated with 5xFAD. Materials and methods5 × FAD mice underwent a 12-week EA treatment regimen. The efficacy of EA against 5 × FAD was assessed through in vivo experiments, including Morris water maze and contextual fear conditioning tests for learning and memory abilities. Immunofluorescence (IF) and thioflavin staining examined changes in Aβ/neurons in brain tissue. RT‒qPCR evaluated inflammatory cytokine expression, while Bcl2/Bax protein levels were analyzed via Western blot (WB). ResultsEA demonstrates promise in alleviating symptoms associated with 5xFAD. It significantly reduced the mice's escape latency in the Morris water maze, increased the frequency of crossings in the target quadrant, and prolonged freezing time in the contextual fear memory test. EA also improved neuronal pathology in the hippocampus and cortex, decreased neuronal loss, and reduced Aβ levels. Moreover, EA significantly increased MDA and SOD levels, effectively modulated the Bcl2/Bax ratio, and decreased the production of proinflammatory factors in brain tissue of 5xFAD model mice. In conclusionOur findings highlight the potential therapeutic efficacy of EA in addressing 5xFAD-related nervous system disorders by targeting Aβ levels, oxidative stress, and inflammation.